Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 x 2 factorial design to receive dexamethasone (6 mg/m(2)/d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m(2)/d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m(2)/d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous system-directed therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7% +/- 0.8%, compared with 7.1% +/- 1.1% for prednisone (P =.01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% +/- 2% for dexamethasone and 77% +/- 2% for prednisone (P =.002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse.

PURPOSE:The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival.PATIENTS AND METHODS:Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP).RESULTS:The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not.CONCLUSION:EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.

PURPOSE To assess the efficacy of a chemotherapy-only regimen in pediatric patients with disseminated non-lymphoblastic lymphoma and acute B-cell leukemia (B-ALL). PATIENTS AND METHODS Sixty-eight eligible patients with previously untreated disseminated non-lymphoblastic lymphoma were enrolled on a Childrens Cancer Group study. Therapy included cycles of chemotherapy, systemic and intrathecal (IT), ever 3 weeks for a total maximal duration of 57 weeks. Fifty-five patients had small non-cleaved cell lymphoma (SNCCL) and 13 had diffuse large cell lymphoma (DLCL). Forty-seven were stage III, six were stage IV, and 15 had B-ALL; 13 had central nervous system (CNS) involvement. RESULTS Four year event-free survival (EFS) was 53% (SE +/- 12%). Stage III SNCCL patients with LDH < 500 IU/L achieved an improved EFS compared to other SNCCL patients (86% vs. 42% 4 year EFS, P = .072). The primary site of failure for advanced stage SNCCL patients was the CNS. All Ki-1-positive DLCL patients relapsed. Patterns of failure, time to relapse, and outcome following relapse differed between SNCCL and DLCL patients. CONCLUSIONS Advanced stage SNCCL requires better CNS-directed chemotherapy to reduce the CNS failure rate; however, the achievement of durable disease-free survival in four of 11 patients with CNS disease without use of cranial irradiation suggests merit for further evaluation of chemotherapy-only strategies. DLCL patients do not need intensive CNS-directed chemotherapy.

Two males with Down syndrome and acute lymphoblastic leukemia with the acquired translocation, t(8;14)(q11;q32), are described. In each case the constitutional karyotype was 47,XY,+21. The patients were, respectively, aged 3 years 11 months and 32 years, with presenting white blood counts 34 and 1.9 x 10(9)/L with blasts of FAB L1 and L2. In each case immunophenotype of the blasts was C-ALL. The child is alive and well and in first remission 6 years from diagnosis. In contrast, the adult patient died in first remission 8.5 months from diagnosis with severe pancytopenia. These are to our knowledge the second and third cases of ALL with t(8;14)(q11-12;q32) associated with a constitutional genetic disorder.

We report two occurrences of dic(9;12) in acute lymphoblastic leukemia and review previous cases. Cases of dic(9;12) share common features with cases of 9p and 12p rearrangements, but prognosis seems particularly good in cases of dic(9;12). The persistence of a specific dicentric in stable clones is remarkable and points to unusual centromeric behavior and/or marked selective advantage of the anomaly.

The short-term and long-term effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) in improving muscle mass (arm muscle area [AMA]) was evaluated for 24 malnourished children with newly diagnosed Stage IV neuroblastoma (n = 14) or Stages II-V Wilms' tumor (n = 10). Patients were randomized to either CPN or PPN plus enteral nutrition (EN: intense nutrition counseling, oral foods, and supplements) for 4 weeks followed by EN until week 10. Oncologic treatment was similar for each tumor type. Dietary, anthropometric, and biochemical measurements were obtained at weeks 0, 4, and 10. During weeks 1 through 4, energy (CPN: means 100 +/- 4; PPN: means 96 +/- 4% of healthy children) and protein (CPN: means 2.5 +/- 0.1; PPN means 2.7 +/- 0.2 g/kg) intakes of the two groups did not differ. The AMA increased (P less than 0.05) with 4 weeks of CPN but not with PPN; changes thereafter with EN were not significant. Weight (P less than 0.05) and triceps skinfolds (P less than 0.01) increased with 4 weeks of PN in both groups and decreased with EN thereafter (P less than 0.01) but were higher at week 10 than diagnosis. Increases in albumin in both groups reached significance at week 10 (P less than 0.05). These data show that CPN improves AMA in malnourished children with neuroblastoma or Wilms' tumor when energy and protein intakes are adequate. The AMA gains can be maintained thereafter with EN.

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0–4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P < 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.

The present study is a detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) (78 B lineage and 26 T lineage) cases. Clonal chromosomal abnormalities were found in marrow blasts from 77 of 104 (74%) cases. Hyperdiploidy was much more frequent in B-lineage ALL cases, whereas normal diploidy was more common in T-lineage ALL cases. Fifty-nine of 104 cases (46 of 78 B-lineage ALL and 13 of 26 T-lineage ALL cases) had structural chromosomal abnormalities. Structural abnormalities involving 2p11, 7p13, 7p22, proximal q arm of 7 (7q11 or 7q22), 11q23–24, and translocations involving 12p11–13 appeared to be B- lineage specific. By comparison, structural abnormalities involving 7p15, 7q32, and 14q11 displayed T-lineage specificity. Structural abnormalities involving 9p22-p23 or 14q32, del (6)(q21-q23), del (12)(p11-p13), and the Philadelphia chromosome were found in B-lineage as well as T-lineage ALL cases. This study expands the current knowledge about immunophenotype-karyotype associations in ALL.

This report evaluates the efficacy of extensive chest wall resection and prosthetic reconstruction in 15 children with chest wall malignancies. There were nine boys and six girls, with a mean age of 9.6 years. Eleven patients had primary chest wall tumors including Ewing's sarcoma (ES), six; rhabdomyosarcoma (RH), two; chondrosarcoma (CS), one; Askin's malignant neuroectodermal tumor, one; and mesenchymal sarcoma, one. Four children had metastases to chest wall and lung from Wilms' tumor (WT), two; osteogenic sarcoma (OS), one; and neuroblastoma (NB), one. Chest wall resection of two to six ribs and reconstruction with Marlex mesh (seven), lattisimus flap (two), prolene mesh (one), and more recently, a Gortex patch (five), was performed. Eight of the patients required concomitant en-bloc pulmonary resection (wedge, five; lobectomy, two; pneumonectomy, one) and two required resection of diaphragm. Fourteen received adjunctive therapy (chemotherapy, 14; irradiation, eight [preoperative, five; postoperative, three]. Six patients had second-look resections after chemotherapy. There was no operative mortality. Early pulmonary function was normal; however, pulmonary restrictive disease and scoliosis occurred with growth. One ES patient developed a radiation-induced second malignant tumor at age 10 and one ES child died at age 6 (no evidence of disease) of meningitis. Average survival length for ES patients was 77 months (range, 18 to 132 months.) Currently, eight patients are alive and five are free of disease. Extensive chest wall resection and reconstruction is useful in the treatment of primary chest wall tumors, but is palliative in metastatic cases. The Gortex patch is the current prosthetic of choice.

Colony assays were performed for 50 patients with B cell precursor acute lymphoblastic leukemia (ALL). Blast colony formation was observed for 33 patients, and the plating efficiency (PE) showed a marked interpatient variation, which indicates a pronounced biological heterogeneity at the level of leukemic progenitor cells. Notably, the mean PE of leukemic B cell precursors from patients with a pseudodiploid or near-diploid karyotype with structural chromosomal abnormalities (SCA) was significantly higher than the mean PE of normal diploid or hyperdiploid cases. All patients who had SCA involving 7p13, 11q23-24, or 12p11-13, and patients with a Philadelphia chromosome had high PE values. The S phase percentage, expression of CD19 antigen, and relapse status were also correlated with PE. Significantly, colony blasts had slightly different surface marker profiles in each case and were common ALL antigen negative in 33% of cases, which indicates the existence of a marked immunological heterogeneity at the level of leukemic progenitor cells.

One hundred thirty-nine children with neoplasms were studied using magnetic resonance imaging (MRI). This procedure was as accurate as computed tomography in predicting tumor histology, except that MRI was unable to detect small areas of tumor calcification. Magnetic resonance imaging could accurately identify the organ of origin of tumor masses and differentiate soft tissue from fat, fluid, or hemorrhage. In addition, MRI was helpful in planning surgery in many cases: It was better than computed tomography in defining the size and extent of soft-tissue tumor masses. It was accurate in defining the extent of the spread of bone sarcomas in the bone marrow. Without requiring the injection of intravenous contrast agents, it accurately defined displacement, encasement, or invasion of major abdominal blood vessels by Wilms' tumors and neuroblastomas. As a means of evaluating pediatric neoplasms, MRI is noninvasive, painless, and well tolerated by children, and it uses no radiation.

Sequential high-dose cytosine arabinoside (ara-C) and asparaginase were given to 41 children age six months to 21 years of age with advanced leukemia. Ten of 22 patients with acute lymphocytic leukemia (ALL) and eight of 19 patients with acute nonlymphocytic leukemia (ANLL) obtained complete remissions. The most significant toxicity seen was infection in 22 patients. In addition, patients given intrathecal chemotherapy within 24 hours of ara-C developed neurologic toxicity. The high response rate seen in these patients with advanced leukemia indicates that a trial of this regimen is warranted in children with less advanced ALL and ANLL.

The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

In the last decade, advances were made in understanding the significance of protein energy malnutrition (PEM), in recognizing PEM in specific subpopulations of children with malignancies, in Staging and assessment of nutritional status, and in understanding the efficacy and limitations of various options for nutrition support. This report describes our experience in providing nutrition support for over a 100 children with newly diagnosed malignancies who have been monitored carefully on study protocols and treated at a single pediatric cancer facility. This work was possible because of the close collaboration between the Departments of Pediatric Hematology Oncology, Pediatric Surgery, Radiation Oncology, and Pediatric Nutrition and Dietetics at James Whitcomb Riley Hospital for Children.

S ummary Recurrent leukaemia following bone marrow transplantation is most often due to the regrowth of original host leukaemia cells, but may also be due to the malignant transformation of normal donor marrow cells after transplantation into a leukaemia patient. We report the ninth case of malignant change in cells of donor origin in a 12‐year‐old boy who was originally diagnosed as having Ph 1 + CML. He remained Ph 1 + during lymphoid blast crisis. After transplantation with marrow from a cytogenetically normal sister, he relapsed to Ph 1 – ALL in the female donor cells. The marrow showed a mixed karyotype of 46,XX/46,XX,inv(9)(p12q12). It would appear that, haematologically, the patient showed different manifestations of the same disease state. Cytogenetically, however, the pre‐ and post‐transplant leukaemias were different.

Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumor as well as CT. MRI showed marrow abnormality in four children who had leukemia.